Abstract
Many genetic factors are involved in the pathogenesis of rheumatoid arthritis (RA). This study is aimed to summarize the literature regarding the relationship between variation in the genes encoding NLRP3/CARD8 and RA, using a candidate polymorphism approach. Several investigations have been conducted on the association of the genetic alterations of the NLRP3 p.Q705K and CARD8 p.C10X with the inflammatory diseases. Although there are variable results, the role of inflammatory pathways and genes involved is undeniable. The genetic context of the NLRP3 p.Q705K and CARD8 p.C10X gene variants in the pathogenesis of RA is still unclear to confirm that these variations show a pivotal role in the pathophysiology of RA. More comprehensive studies in this area seem to be needed.
Highlights
SNP locusHLA DRB1 allele ( known as the shared epitope) involved in MHC molecule–based antigen presentation and responsible for self-peptide selection and T-cell repertoire; first discovered and still by far the strongest genetic link to rheumatoid arthritis[13]
Some evidence proposes that the NLR family pyrin domain containing 3 (NLRP3) p.Q705K and CARD8 p.C10X genetic variants are likely to influence the progression of Rheumatoid arthritis (RA)
It is important to note that reviewing of functional characteristics of SNPs in complex diseases with high environmental and genetic factors is a challenge that affects the pathophysiology of the disease
Summary
HLA DRB1 allele ( known as the shared epitope) involved in MHC molecule–based antigen presentation and responsible for self-peptide selection and T-cell repertoire; first discovered and still by far the strongest genetic link to rheumatoid arthritis[13]. Among several cytokines, ‘IL-1β’ released from monocytes and macrophages play a critical role in the propagation of the chronic inflammatory process in the joints of rheumatoid patients.[28] The findings show that in arthritis, different proteases including protease 3, elastase, and mast cell kinase can be secreted by leukocytes, which are effective in the maturation of pro-IL-1β into an active form.[29,30] On the other hand, in the synovial tissues of RA patients, myeloid and endothelial cells are the main sources of IL-1β and interleukin 1 alpha (IL-1α) production. It is a gainof-function change in exon 3 of the NLRP3 gene, a low penetrant variant, which increases the production of IL-1β
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